Related Experiment Video
Updated: Jul 18, 2025
09:01
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
423
BCL2 Inhibition Reveals a Dendritic Cell-Specific Immune Checkpoint That Controls Tumor Immunosurveillance.
Liwei Zhao1,2, Peng Liu1,2, Misha Mao1,2,3,4
1Centre de Recherche des Cordeliers, Equipe Labellisée par la Ligue contre le Cancer, Université de Paris, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Cancer Discovery
|August 25, 2023
Summary
Targeting BCL2 enhances dendritic cell (DC) function, improving anti-tumor immunity. BCL2 inhibition acts as a DC-specific immune checkpoint, sensitizing solid tumors to immunotherapy.
Area of Science:
- Immunology
- Cancer Biology
- Cellular Biology
Background:
- Dendritic cells (DCs) are crucial for initiating anti-tumor immune responses.
- BCL2 is identified as a key regulator of DC function.
Purpose of the Study:
- To investigate the role of BCL2 in DC function and anti-tumor immunity.
- To explore the therapeutic potential of BCL2 inhibition in cancer treatment.
Main Methods:
- Genome-wide CRISPR screen to identify regulators of DC function.
- Utilized pharmacologic BCL2 inhibitors (venetoclax, navitoclax).
- Assessed DC antigen presentation, activation, and tumor control in mouse models.
Main Results:
- BCL2 knockout enhanced DC antigen presentation, activation, and tumor control.
- Pharmacologic BCL2 inhibition mimicked these effects, leading to tumor regression.
- Therapeutic efficacy was dependent on CD103+ dendritic cells (cDC1) and T cells.
- BCL2 inhibition sensitized solid tumors to PD-1 blockade immunotherapy.
Conclusions:
- BCL2 acts as a DC-specific immune checkpoint.
- Targeting BCL2 enhances DC-mediated anti-tumor immunity.
- BCL2 inhibition is a promising strategy to sensitize solid tumors to immunotherapy.
Related Concept Videos
01:27Tumor Immunotherapy
556
Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
556
01:22T Cell Activation and Clonal Selection
806
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
806
01:27Cytotoxic T Cells-mediated Immune Response
965
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
965
02:34Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
01:31The Intrinsic Apoptotic Pathway
6.6K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.6K
02:23Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K